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Chondrosarcoma of the radius with distant metastasis in a dog.

A 9-year-old castrated male Doberman Pinscher was admitted for evaluation of lameness of the left forelimb. Radiography and examination of biopsy specimens revealed a moderately differentiated chondrosarcoma of the proximal portion of the radius. The dog was treated by local excision of the neoplasm, which involved resection of the radial head and proximal portion of the radius. Despite the large size of the dog and the weight-bearing forces exerted on the cubital joint, major problems with ambulation did not develop after surgery. Functional use of the limb returned slowly; however, substantial limb use was observed despite the development of mild degenerative changes of the joint and migration of the humeroulnar articulation. Six months after surgery, metastasis of a widely disseminated, poorly differentiated chondrosarcoma to the subcutaneous tissues and thoracic and abdominal cavities was diagnosed. Local redevelopment of the chondrosarcoma in the area of the cubital joint was not detected. Resection of the radial head and proximal portion of the radius may be considered a viable, alternative, limb-sparing technique. The biologically aggressive nature of this chondrosarcoma of the appendicular skeleton indicated that additional information was needed before a reliable prognosis could be established for this dog with this tumor type. Reports of low rates of metastasis have been based on insufficient numbers of dogs to adequately or accurately determine the long-term prognosis of dogs with chondrosarcoma of the appendicular skeleton.

Adrenal Gland Neoplasms↗

Reproductive outcomes among Mexico-born women in San Diego and Tijuana: testing the migration selectivity hypothesis.

Mexican immigrants to the United States have better reproductive outcomes than do U.S.-born non-Latina whites. Explanations offered for this "epidemiologic paradox" include (1) poor outcomes among Mexican women may be hidden by their return to Mexico; (2) Mexican women may have a higher fetal death rate that alters the pattern of live birth outcomes; (3) Mexican women may have socioeconomic characteristics which, if properly measured, would explain the outcome; (4) Mexican women may have personal characteristics which would explain the outcome, if properly measured; (5) there may be ameliorative or salutogenic "protective" effects of culture; and (6) migration may be selective of healthier women who are thus more prone to positive outcomes. We test these explanations, with an emphasis on the last one, using a data set that combines reproductive histories and birth outcomes for Mexico-born women delivering in San Diego, California and Mexican women delivering in Tijuana, Mexico. These data are compared with U.S.-born Latinas and U.S.-born non-Latina Whites. Multivariate logistic regression analysis suggests that when controlling for birth history (stillbirths and miscarriages), socioeconomic characteristics (education and prenatal visits), personal characteristics (age, parity, time in area, history of family problems), and health characteristics (history of smoking, alcohol use, drug use, anemia, vaginal bleeding, urinary infection), the adjusted odds of a positive birth outcome (measured as a live birth of 2500 grams or more) is highest for women delivering in Tijuana, implying that migrants may not be so selective when compared to the country of origin. The number of prenatal visits was an important explanatory variable.

Journal Article↗

An alternatively spliced form of Pit-1 represses prolactin gene expression.

The pituitary-specific transcription factor Pit-1 is required for expression of the PRL gene. Transcription of the PRL gene in the anterior pituitary is both activated and repressed in response to neuroendocrine signals. The molecular events that mediate repression are unknown. Transplantation of GH3 pituitary tumor cells from culture to female Wistar-Furth rats resulted in repression of PRL gene expression. When the transplanted cells were returned to culture, PRL gene expression was rapidly activated. We used this model to study potential mechanisms by which PRL gene expression was silenced. In addition to the appropriate size Pit-1 proteins of 33 and 31 kilodaltons, smaller forms of the transcription factor, migrating at approximately 27 and 24 kilodaltons, were found in transplanted cells in which PRL gene expression was repressed. These smaller forms of Pit-1 protein were observed to disappear when transplanted cells were returned to culture, coincident with the activation of PRL gene expression. A transcript approximately 170 base pairs shorter than expected for that encoding full-length Pit-1 was detected in transplanted GH3 cell RNA by polymerase chain reaction. The shorter Pit-1 transcript was abundant only in GH3 cells after in vivo passage and was not readily detected in transplanted cells after as little as 12 h in culture. This shorter transcript was found to result from excision of sequence corresponding to exon IV and encodes a Pit-1 protein lacking 54 amino acids of the POU-specific domain. Gene transfer studies demonstrated this alternative form of Pit-1 inhibited PRL promoter activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Female migration in Chile: types of moves and socioeconomic characteristics.

This paper examines inter-provincial female migration in Chile for the 1965--1970 period, with a view to describing socioeconomic characteristics of migrant women and to determining differences and similarities in age, educational level, occupation, and type of move (first, return, or repeat) between movers to the capital and to other urban areas. Data are from a five percent sample of the 1970 Chilean census. Findings reveal that non-return migrants to other urban areas are differentiated from those to Santiago by an older age structure, higher educational levels, higher status occupations, and are more likely to be making a second (or higher-order) move. Moreover, educational measures suggest that recent female migration to urban Chile is more prevalent among the upper than the lower strata of the society.

Adolescent↗

[Migration and uneven aging in the regions of France].

Regional differences in the rate of demographic aging in France are examined. The author notes that "contrary to popular belief, of the two factors that contribute to aging, natural trends (births and deaths) still have the edge over the effect of population migrations across regions. The only exception to this is in the Paris area, due to the influence of Paris itself, where youthfulness caused by migrations is on a more or less equal footing with 'natural' aging. Conversely, migration contributes the most to the increase in the average age in the western French regions, with the joint effects of young people leaving and the over-60s returning." (SUMMARY IN ENG AND GER AND SPA)

Age Distribution↗

Lymphocyte traffic through chronic inflammatory lesions: differential migration versus differential retention.

Afferent lymphatics draining granulomas and efferent lymphatics from normal lymph nodes were cannulated in sheep. Cells collected from these lymphatics were radiolabelled in vitro with 111In (afferent lymph cells) and 51Cr (efferent lymphocytes) and both labelled cells were returned to the animal simultaneously by i.v. injection. The reappearance of these labelled cells in lymph, and the amount of 111In and 51Cr in normal or antigenically stimulated lymph nodes, cutaneous inflammatory sites (FCA-granulomas, NLT- and BCG-induced lesions) and blood was determined 24 hr later. As previously reported, labelled afferent cells preferentially migrated from the blood back through the granuloma into afferent lymph, and efferent lymphocytes back into efferent lymph. Forty per cent as many 111In- as 51Cr-labelled cells ;appeared in efferent lymph. This was caused by the greater migration of 51Cr-labelled cells appeared in efferent lymph. This was caused by the greater migration of 51Cr- than 111In-labelled cells out of the blood into the node. Neither cell type was selectively retained in the node, and 28% of the labelled cells that entered the node migrated on into efferent lymph in 24 hr. Similarly, there was no selective retention of either cell type in the granuloma, and equal amounts of 111In the 51Cr appeared in afferent lymph. The ratio 111In/51Cr in the blood suggested that in the lymph node the two labelled cell populations were extracted equally, while in the granuloma selectively at the level of the vascular endothelium resulted in the preferential extraction of 111In-labelled (afferent lymph) cells.

Animals↗

How does HIV cause depletion of CD4 lymphocytes? A mechanism involving virus signaling through its cellular receptors.

HIV infection causes an acquired immunodeficiency, principally because of depletion of CD4 lymphocytes. The mechanism by which the virus depletes these cells, however, is not clearly understood. Since the virus predominantly infects CD4 lymphocytes in vivo, some have assumed that HIV replication directly kills the infected cells or that the anti-HIV immune response destroys them. However, a large number of studies do not support this concept. Rather, the data strongly indicate that CD4 lymphocyte depletion is by an indirect mechanism. Several theories on various direct and indirect mechanisms are reviewed. The most plausible mechanism, which is backed by in vivo data, involves the consequences of HIV contact with resting CD4 lymphocytes, which cannot support virus replication. HIV binding to, and signaling through, CD4 and chemokine receptor molecules on resting CD4 lymphocytes and other cell types [which extensively occurs as the rare, productively infected cells (ie: infected cells producing virus) migrate among other cells through the lymphoid tissues back into the blood] induces upregulation of L-selectin and Fas. When these resting, HIV-signaled CD4 cells return to the blood, they home very rapidly back to peripheral lymph nodes and axial bone marrow, and their disappearance from the blood is likely due to their leaving the circulatory system. Approximately one-half of these cells that have been induced by HIV to home to lymph nodes are subsequently induced into apoptosis during the process of trans-endothelial migration when secondary signals are received through various homing receptors. These cells are not making HIV, which would explain the observation that CD4 cells not making HIV are the predominant cells dying in the lymph nodes of HIV+ subjects. These studies indicate that the principal mechanism of CD4 T-cell depletion by HIV is due to its use of CD4 as its primary receptor and the signaling induced through this receptor on nonpermissive (resting) T-lymphocytes. This unique mechanism of viral pathogenesis, if correct, leads to the possibility that HIV might not cause depletion of CD4 lymphocytes if it used some other receptor to infect CD4 lymphocytes.

CD4-Positive T-Lymphocytes↗

Injury of stromal fibroblasts induces phosphorylation of focal adhesion proteins.

PURPOSE: The extracellular matrix serves as a structural support for the corneal stroma and mediates signaling events that regulate the intracellular environment of stromal keratocytes. We hypothesize that adhesion and injury mediate signal transduction events causing the phosphorylation of tyrosine residues of specific adhesion proteins and that phosphorylation is required for cellular adhesion and migration. METHODS: For the adhesion experiments; primary rabbit stromal fibroblasts were seeded and phosphorylation of tyrosine residues was followed from 1 min to 24 h. For the injury experiments, confluent primary cultures were rendered quiescent, wounded, and tyrosine phosphorylation was followed from 30 s to 6 h. The antibody (py-20) was used to detect proteins phosphorylated on tyrosine residues. We examined changes in the phosphorylation of focal adhesion kinase (FAK), paxillin and cortactin, using immunoprecipitation and Western blot analysis. RESULTS: In the adhesion experiments, the phosphorylation of a 68-kDa protein was detected after 1 min, and the phosphorylation of a 125-kDa protein was not detected until 15 min. These proteins were identified in re-probed blots as paxillin and FAK. In the injury experiments, FAK phosphorylation was detected within 30 s and remained elevated for 6 h when cells were cultured on fibronectin. Both FAK and paxillin phosphorylation were prominent after injury, but unlike FAK phosphorylation, paxillin phosphorylation decreased over time. Phosphorylation was prominent at the wound margin. After wound closure, it returned to background levels. Tyrosine kinase inhibitors, genistein and herbimycin, decreased the number of adherent cells and altered the rate of cell migration after injury, compared to control (DMSO alone). CONCLUSION: The results indicate that injury and cell-matrix interaction mediate the phosphorylation of specific adhesion proteins and that phosphorylation is required for wound repair.

Animals↗

An intravascular chemoattractant lectin inhibits neutrophil migration.

KM+, a lectin purified from Artocarpusintegrifolia seeds, is an attractant for neutrophils, and has properties similar to fMLP, IL-8 and MNCF. The endogenous lectin MNCF, inhibits carrageenan-induced neutrophil migration when intravenously administered in rats. In an attempt to mimic the activity of MNCF with KM+, we determined the effect of intravenous (iv) injection of KM+ (5 microg) on neutrophil migration to the peritoneal cavity of Wistar rats induced by KM+ (50 microg, intraperitoneal, ip), fMLP (5 ng, ip) and carrageenan (300 microg, ip). Initially we evaluated the effect of the time interval between intravenous and intraperitoneal administration of KM+. The intervals ranged from 20 to 120 min and progressively stronger inhibition was observed with increasing time intervals up to a maximum of 60 min, with effect decreasing thereafter. With injections at the optimum interval of 60 min, we observed that KM+ inhibited KM+- and carrageenan-induced neutrophil migration by 72%, and fMLP-induced migration by 56%. White cell counts for Wistar rats that only received KM+iv, performed at 0 to 120 min intervals after injection, revealed early neutropenia lasting 60 min, followed by a marked increase in circulating neutrophils that reached a maximum of twice the initial levels within 90 min and after 120 min returned to levels near to that observed before intravenous administration of KM+. These results indicate that when KM+ is present in the intravascular space, it produces an inhibitory effect on neutrophil migration similar to that caused by the intravenous administration of other chemoattractants, regardless of whether they act through a mechanism independent of carbohydrate recognition, as does IL-8, or are dependent on carbohydrate recognition, like MNCF.

Animals↗

Leucocyte migration inhibition in cow's milk protein intolerance.

The leucocyte migration inhibition (LMI) was determined in an assay after in vitro challenge with beta-lactoglobulin. The assay was considered positive when migration inhibition index was greater than 20% (mean +3 SD of healthy infants). Ninety-eight infants with protracted diarrhoea and failure to thrive, 16 healthy, 12 malnourished, and 16 infants suffering from acute gastroenteritis were studied. Of the 98 patients with protracted diarrhoea, 12 fulfilled Goldman's criteria for cow's milk protein intolerance, 63 had lactose malabsorption, and in 15 no associated causative factor was identified. The mean index of migration inhibition in the cow's milk allergic group (58.83 +/- 11.98) was higher than in healthy controls (8.25 +/- 3.91), the difference being statistically significant (p less than 0.05). The test was positive in all patients with cow's milk protein intolerance. The assay was also positive in four other patients suffering from protracted diarrhoea, two of whom had lactose malabsorption. All the infants with acute gastroenteritis and malnutrition had values within the normal range. The migration inhibition index in five patients with cow's milk intolerance had declined to 24.74 +/- 4.87 in assays performed 1-6 weeks after return of clinical tolerance to cow's milk (p less than 0.05) but the test was still within the positive range in three of the five infants. These results suggest that this cell mediated immune assay is a sensitive test for the diagnosis of cow's milk protein intolerance in infants. The specificity needs to be reassessed in the light of more objective criteria for the diagnosis of cow's milk protein intolerance.

Animals↗

Migratory shearwaters integrate oceanic resources across the Pacific Ocean in an endless summer.

Electronic tracking tags have revolutionized our understanding of broad-scale movements and habitat use of highly mobile marine animals, but a large gap in our knowledge still remains for a wide range of small species. Here, we report the extraordinary transequatorial postbreeding migrations of a small seabird, the sooty shearwater, obtained with miniature archival tags that log data for estimating position, dive depth, and ambient temperature. Tracks (262+/-23 days) reveal that shearwaters fly across the entire Pacific Ocean in a figure-eight pattern while traveling 64,037+/-9,779 km roundtrip, the longest animal migration ever recorded electronically. Each shearwater made a prolonged stopover in one of three discrete regions off Japan, Alaska, or California before returning to New Zealand through a relatively narrow corridor in the central Pacific Ocean. Transit rates as high as 910+/-186 km.day-1 were recorded, and shearwaters accessed prey resources in both the Northern and Southern Hemisphere's most productive waters from the surface to 68.2 m depth. Our results indicate that sooty shearwaters integrate oceanic resources throughout the Pacific Basin on a yearly scale. Sooty shearwater populations today are declining, and because they operate on a global scale, they may serve as an important indicator of climate change and ocean health.

Animal Identification Systems↗

The nonmetropolitan population turnaround.

From 1970-1980, US nonmetropolitan areas grew more rapidly than previously, achieving overall a faster growth rate than metropolitan areas, with more migrants going from metropolitan to nonmetropolian areas than in the opposite direction. This paper reviews the literature that has emerged in seeking to understand this new trend, which was contrary to expectations and became known as the nonmetropolitan turnaround. Work includes macroanalyses of changes in nonmetropolitan settlement structure, changes in the distribution of employment, migration streams and differentials, as well as research on residential preferences and migration decison making. This is a new trend in terms of population distribution processes, although evidence that it reflects a greater importance of noneconomic factors in migration is mixed. Nonmetropolitan growth slowed in the latter part of the 1970s and overall the turnaround reversed in the early 1980s, but a return to a generally concentrated settlement pattern appears unlikely. The amount of research accomplished over a short span of time as a consequence of the turnaround is noteworthy, and the findings have contributed to increased understanding of US population change.

Americas↗

ATP-induced CA2+-signaling enhances rat gastric microvascular endothelial cell migration.

The effects of exogenous ATP on Ca2+ signaling and wound healing were investigated in rat gastric microvascular endothelial cells (RGMEC). ATP (10 microM) triggered a significant rise in intracellular Ca2+ concentration ([Ca2+]i) from 46+/-2 nM at baseline to peak values averaging 283+/-31 nM (n = 5 experiments, 132 cells). Return to the basal [Ca2+]i was delayed by slowly declining plateau phase that persisted for 200+/-30 s. Removal of extracellular Ca2+ did not significantly affect the peak rise in [Ca2+]i, but reduced the plateau. ATP (10 microM) also significantly increased the migration of RGMEC in a wounded monolayer. Addition of the non-subtype selective purinergic receptor antagonist, suramin, abrogated the effects of ATP on [Ca2+]i and migration. We conclude that local elevation of ATP acting through purinergic receptors induce Ca2+ signals in RGMEC and may contribute to endothelial cell migration.

Adenosine Triphosphate↗

Auxiliary heterotopic liver transplantation in the rat: a simplified model using cuff technique and application for congenitally hyperbilirubimemic Gunn rat.

To study the immunological and metabolic effects of auxiliary liver transplantation (ALT), a simple ALT model in rats was developed using the cuff application. Effects of transient parking of normal liver were tested in congenitally hyperbilirubinemic Gunn rats. Serum bilirubin concentrations in Gunn rats, transplanted heterotopically with normal livers of Wistar rats, were dramatically reduced and maintained within normal levels. The graftectomy was performed safely 1 month after transplantation, but total bilirubin levels did not return to the preoperative value of the Gunn rats. It is possible that hepatic stem cells included in ALT liver migrated to the host liver and differentiated into cells capable of producing certain enzymes.

Analysis of Variance↗

Cholesterol movement between bovine rod outer segment disk membranes and phospholipid vesicles.

The ability of cholesterol to move between bovine rod outer segment disk membranes and phospholipid membranes was examined. Disk membranes were incubated with small unilamellar phospholipid vesicles containing varying amounts of cholesterol. Aliquots were removed at specific times, and then the disks and the vesicles were separated by centrifugation and assayed for phospholipid and cholesterol content. When incubated with vesicles containing no cholesterol, the cholesterol to phospholipid ratio in the disk membrane was reduced due to migration of cholesterol from the disks into the vesicles. The cholesterol content of these cholesterol depleted disks could be readily returned to the normal disk cholesterol content by incubation of the cholesterol-depleted disks with small unilamellar vesicles containing high cholesterol. An apparent partition coefficient K was calculated as the quotient of the cholesterol/phospholipid mole ratio in the donor membranes and the cholesterol/phospholipid mole ratio in the acceptor membranes. The value of K was approximately 1 at cholesterol levels below normal disk cholesterol content, for disk membranes and phosphatidylcholine small unilamellar vesicles. Inclusion of phosphatidylethanolamine in the small unilamellar vesicle acceptor raised K, indicating that phosphatidylethanolamine creates an unfavourable environment for cholesterol. The cholesterol to phospholipid ratio of native disks could be increased by incubation with phosphatidylcholine small unilamellar vesicles (donor) which contained higher amounts of cholesterol than the disk membrane acceptor. In these experiments the distribution of cholesterol between disks and small unilamellar vesicles always favored the vesicles. The apparent partition coefficient was 1.7 at several cholesterol levels above the native disk cholesterol content. Liposomes made from lipid extracted from the disk membrane behaved in the same manner as intact disks with respect to cholesterol distribution at equilibrium. The phospholipid content of the disk membrane may be an important factor in determining the cholesterol content of the disk membrane.

Animals↗

Short report: migration among persons living with HIV.

Data from the first national probability sample of persons with HIV, the HIV Cost of Services and Utilization Survey (HCSUS), are used to examine migration patterns among persons with HIV/AIDS in the USA. Persons with serious illness may choose to relocate to receive better care or support. This migration has implications for the distribution of resources. This study describes the frequency and reasons that persons with HIV move to different communities. An analytic file of 3014 respondents was obtained from the first national probability sample of persons with HIV/AIDS, the HCSUS. A migration section of the baseline questionnaire questioned respondents on their residential history. Persons were defined as movers if they moved across state lines or to a non-contiguous county after knowing they were HIV positive but before the HCSUS baseline interview. Forty percent of movers said that their HIV status was a very important factor in their decision to move. Although earlier studies of limited generalizability found movement among the HIV population from urban to rural counties, this study found only eight percent of HIV migration was from urban to rural counties, just slightly more than the migration from rural to urban counties. In addition, the vast majority of people who were moving were not moving to return home. Major factors in the decision to move included being near caregivers and being in a community with shared needs and interests. Significant numbers of persons also moved to obtain care from a physician knowledgeable in HIV treatment or to get away from discrimination. Financial assistance and the availability of Medicaid also played a prominent role in many decisions to move. Persons with HIV/AIDS are more likely to move than non-infected persons in the general population. Moreover, they are almost twice as likely to be moving out-of-state. Persons with HIV who move are similar to persons with HIV who do not move on most demographic characteristics including age, region of the country, and income.

Adult↗

Increased PDX-1 expression is associated with outcome in patients with pancreatic cancer.

BACKGROUND: During pancreatic development, pancreatic duodenal homeobox gene-1 (PDX-1) is expressed in pancreatic duct cells that have the potential to differentiate into islets. Therefore, PDX-1 is thought to be a marker of de-differentiated cells with the capacity to redifferentiate into several pancreatic cell types. We analyzed PDX-1 expression in human pancreatic cancer specimens, pancreatic cancer cell lines, and the effects of forced expression of PDX-1 in pancreatic cancer cells. METHODS: Thirty-five pancreatic adenocarcinomas were immunohistochemically stained with a polyclonal rabbit antibody against mouse PDX-1. Correlations with tumor characteristics were made with chi-squared analysis. The influence of clinicopathologic factors on survival was assessed. The expression of PDX-1 in pancreatic cancer cells was examined. Replication-deficient recombinant adenoviruses were constructed by the cosmid-adenoviral DNA terminal protein complex method. PANC-1 cells were infected with Ad-pdx-1 or Ad-LacZ. PANC-1 cells that were infected with adenovirus were used in a cell growth assay and a migration assay and for morphologic analysis. RESULTS: Interestingly, 43% of pancreatic cancers were positive for PDX-1 expression, and 57% of pancreatic cancers were negative (normal pancreatic exocrine tissue shows little or no staining for PDX-1). Lymph node metastasis (P =.02) and histologic grade (P =.04) were correlated significantly with PDX-1 expression. Patients with positive PDX-1 had a significantly worse prognosis than those patients with negative PDX-1 (P =.02). Importantly, PDX-1 was an independent variable that effected overall survival (P =.03). Pancreatic cancer cell lines showed no PDX-1 expression. There were no significant differences in cell proliferation or morphologic condition between Ad-pdx-1- and Ad-lacZ-infected PANC-1 cells. However, Ad-pdx-1-infected PANC-1 cells did show a significantly higher migration rate than Ad-lacZ-infected PANC-1 cells. CONCLUSIONS: Re-expression of PDX-1 may represent a return to a more de-differentiated state by more aggressive pancreatic cancers and may also represent an important new tumor marker for these aggressive cancers.

Aged↗